Improvement of the PapMV Nanoparticle Adjuvant Property Through an Increased of Its Avidity for the Antigen [Influenza NP]

Vaccine. 2012 Mar 28;30(15):2535-42. doi: 10.1016/j.vaccine.2012.01.085. Epub 2012 Feb 8.

Abstract

The principal caveat of existing influenza vaccine is their failure to provide long-term protection. This lack of efficiency is caused by persistent (drift) and dramatic (shift) antigenic changes on the major surface proteins, the main target of protective immunity generated by traditional vaccines. Alternatively, vaccination with most conserved protein, like the nucleoprotein (NP) can stimulate immunity against multiple serotypes and could potentially provides an extended protection. The NP antigen contains more than 90% protein sequence homology among influenza A isolates and it also contains dominant CTL targets epitopes that made this antigen an attractive target for developing universal vaccine. However, NP protein is a weak antigen and need the use of adjuvant to increase its immunogenicity. We have developed an innovative high avidity VLP (HAV) nanoparticle to improve its adjuvant property to the NP antigen. The nanoparticles are derived from papaya mosaic virus capsid protein (PapMV CP) produced in a bacteria expression system. We generated the HAV by adding an affinity peptide directed to the NP protein at the surface of the VLPs. The fusions of the affinity peptide to PapMV VLPs increased the avidity of PapMV VLPs to NP protein. This modification enhanced the humoral and the IFN-γ response directed to NP. Moreover, the immunity generated by the HAV adjuvanted NP vaccine improved the protection of vaccinated mice to a challenge with influenza virus. The protection was characterized by accelerated virus elimination after the onset of infection and rapid recovery of the vaccinated animals.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / metabolism*
  • Animals
  • Capsid Proteins / chemistry
  • Capsid Proteins / immunology*
  • Capsid Proteins / metabolism
  • Immunity, Humoral
  • Influenza A virus / immunology
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology
  • Influenza Vaccines / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Nanoparticles* / ultrastructure
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Potexvirus / chemistry*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / immunology*
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Th1 Cells / immunology
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / immunology*
  • Viral Core Proteins / metabolism*

Substances

  • Adjuvants, Immunologic
  • Capsid Proteins
  • Influenza Vaccines
  • NP protein, Influenza A virus
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Viral Core Proteins